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Published on: September 12, 2016
Micronized, Heat-Treated Lactobacillus plantarum LM1004 Alleviates Cyclophosphamide-Induced Immune Suppression
Il Seon Jung1, Min Gyu Jeon1, Da Som Oh1
1Centre for Research and Development, LactoMason Co., Ltd., Jinju, Korea.
Insights
Heat-treated Lactobacillus plantarum LM1004 (HT-LM1004) effectively reversed immune suppression in mice. This probiotic enhanced natural killer cell activity, offering a potential therapeutic for immune dysfunction.
Area of Science:
- Immunology
- Microbiology
- Probiotics
Background:
- Cyclophosphamide (CTX) induces significant immunosuppression, impacting immune cell function.
- Lactobacillus plantarum LM1004 is a probiotic with potential immunomodulatory effects.
Purpose of the Study:
- To investigate the immunomodulatory activity of heat-treated Lactobacillus plantarum LM1004 (HT-LM1004) in a CTX-induced immunosuppression mouse model.
- To elucidate the mechanisms underlying HT-LM1004's effects on immune cells, particularly natural killer (NK) cells.
Main Methods:
- Assessed macrophage activity (phagocytosis, nitric oxide production) and cytokine release (TNF-α, IFN-γ, IL-2, IL-12p70) in vitro.
- Administered HT-LM1004 orally to CTX-treated mice and evaluated thymus and spleen indices.
- Measured cytokine levels and NK cell activity against YAC-1 lymphoma cells in vivo.
- Compared the effects of heat treatment alone versus heat treatment with micronization (membrane bioreactor) on NK cell cytotoxicity.
Main Results:
- HT-LM1004 stimulated phagocytic activity and nitric oxide production in macrophages, along with key pro-inflammatory cytokine release.
- Oral HT-LM1004 administration restored thymus and spleen indices in immunosuppressed mice.
- HT-LM1004 treatment increased serum levels of TNF-α, IFN-γ, IL-2, and IL-12p70 and enhanced NK cell activity.
- Micronized HT-LM1004 demonstrated superior NK cell cytotoxicity compared to heat treatment alone.
Conclusions:
- HT-LM1004 effectively reverses CTX-induced immunosuppression by enhancing NK cell function.
- Both heat treatment and micronization contribute to the immunomodulatory efficacy of L. plantarum LM1004.
- HT-LM1004 presents a promising, side-effect-free therapeutic strategy for immune restoration.
Abstract:
The present study investigated the immunomodulatory activity and associated mechanisms of heat-treated Lactobacillus plantarum LM1004 (HT-LM1004) in a cyclophosphamide (CTX)-induced mouse model of immunosuppression. HT-LM1004 induced phagocytic activity and nitric oxide production in RAW264.7 macrophages and stimulated the release of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, and IL-12p70. In mice with CTX-induced immunosuppression, oral HT-LM1004 administration restored thymus and spleen indices, including spleen weight. Consistent with the in vitro results, HT-LM1004 increased TNF-α, IFN-γ, IL-2, and IL-12p70 levels in mice after 14 days of treatment and enhanced the natural killer (NK) cell activity of splenocytes from mice with CTX-induced immunosuppression against YAC-1 lymphoma cells. The method of HT-LM1004 generation influenced this activity: L. plantarum LM1004 grown in a membrane bioreactor, which reduced the size of the cells to <1.0 μm through physical stress (micronization), promoted NK cell cytotoxicity to a greater extent than LM1004 subjected to heat treatment alone. These findings indicate that HT-LM1004 without or with micronization can reverse CTX-induced immunosuppression without adverse side effects by potentiating NK cell function.
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